- Decarboxylative trifluoromethylation of aryl halides using well-defined copper-trifluoroacetate and -chlorodifluoroacetate precursors
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New synthetic routes to (NHC)copper-trifluoroacetate and -chlorodifluoroacetate complexes were developed (NHC = N-heterocyclic carbenes) so baseline reactivity patterns could be established for the decarboxylative trifluoromethylation of organic halides. In the presence of aryl halides, loss of CO2 from these new precursors occurred at 160 °C concurrent with the formation of aryl-CF3.
- McReynolds, Kristen A.,Lewis, Robert S.,Ackerman, Laura K.G.,Dubinina, Galyna G.,Brennessel, William W.,Vicic, David A.
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Read Online
- Cross-Coupling through Ag(I)/Ag(III) Redox Manifold
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In ample variety of transformations, the presence of silver as an additive or co-catalyst is believed to be innocuous for the efficiency of the operating metal catalyst. Even though Ag additives are required often as coupling partners, oxidants or halide scavengers, its role as a catalytically competent species is widely neglected in cross-coupling reactions. Most likely, this is due to the erroneously assumed incapacity of Ag to undergo 2e? redox steps. Definite proof is herein provided for the required elementary steps to accomplish the oxidative trifluoromethylation of arenes through AgI/AgIII redox catalysis (i. e. CEL coupling), namely: i) easy AgI/AgIII 2e? oxidation mediated by air; ii) bpy/phen ligation to AgIII; iii) boron-to-AgIII aryl transfer; and iv) ulterior reductive elimination of benzotrifluorides from an [aryl-AgIII-CF3] fragment. More precisely, an ultimate entry and full characterization of organosilver(III) compounds [K]+[AgIII(CF3)4]? (K-1), [(bpy)AgIII(CF3)3] (2) and [(phen)AgIII(CF3)3] (3), is described. The utility of 3 in cross-coupling has been showcased unambiguously, and a large variety of arylboron compounds was trifluoromethylated via [AgIII(aryl)(CF3)3]? intermediates. This work breaks with old stereotypes and misconceptions regarding the inability of Ag to undergo cross-coupling by itself.
- Demonti, Luca,Mézailles, Nicolas,Nebra, Noel,Saffon-Merceron, Nathalie
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supporting information
p. 15396 - 15405
(2021/10/12)
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- Investigation on the stoichiometry of carbon dioxide in isotope-exchange reactions with phenylacetic acids
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The functionalization of carbon dioxide (CO 2) as a C1 building block has attracted enormous attention. Carboxylation reactions, in particular, are of major interest for applications in isotope labeling. Due to the inexpensive nature of CO 2, information about its stoichiometric use is generally unavailable in the literature. Because of the rarity and limited availability of CO 2isotopomers, this parameter is of concern for applications in carbon-isotope labeling. We investigated the effects of the stoichiometry of labeled CO 2on carbon isotope exchange of phenyl? acetic acids. Both thermal and photocatalytic procedures were studied, providing insight into product outcome and isotope incorporation. Preliminary results on isotope-dilution effects of carbonate bases in photocatalytic carboxylation reactions have also been obtained.
- Audisio, Davide,Goudet, Amelie,Sallustrau, Antoine,Talbot, Alex,Taran, Frederic
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supporting information
(2021/08/10)
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- Methane Generation and Reductive Debromination of Benzylic Position by Reconstituted Myoglobin Containing Nickel Tetradehydrocorrin as a Model of Methyl-coenzyme M Reductase
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Methyl-coenzyme M reductase (MCR), which contains the nickel hydrocorphinoid cofactor F430, is responsible for biological methane generation under anaerobic conditions via a reaction mechanism which has not been completely elucidated. In this work, myoglobin reconstituted with an artificial cofactor, nickel(I) tetradehydrocorrin (NiI(TDHC)), is used as a protein-based functional model for MCR. The reconstituted protein, rMb(NiI(TDHC)), is found to react with methyl donors such as methyl p-toluenesulfonate and trimethylsulfonium iodide with methane evolution observed in aqueous media containing dithionite. Moreover, rMb(NiI(TDHC)) is found to convert benzyl bromide derivatives to reductively debrominated products without homocoupling products. The reactivity increases in the order of primary > secondary > tertiary benzylic carbons, indicating steric effects on the reaction of the nickel center with the benzylic carbon in the initial step. In addition, Hammett plots using a series of para-substituted benzyl bromides exhibit enhancement of the reactivity with introduction of electron-withdrawing substituents, as shown by the positive slope against polar substituent constants. These results suggest a nucleophilic SN2-type reaction of the Ni(I) species with the benzylic carbon to provide an organonickel species as an intermediate. The reaction in D2O buffer at pD 7.0 causes a complete isotope shift of the product by +1 mass unit, supporting our proposal that protonation of the organonickel intermediate occurs during product formation. Although the turnover numbers are limited due to inactivation of the cofactor by side reactions, the present findings will contribute to elucidating the reaction mechanism of MCR-catalyzed methane generation from activated methyl sources and dehalogenation.
- Hayashi, Takashi,Miyazaki, Yuta,Oohora, Koji
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supporting information
p. 11995 - 12004
(2020/09/15)
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- Deoxyfluorination of acyl fluorides to trifluoromethyl compounds by FLUOLEAD/Olah's reagent under solvent-free conditions
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A new protocol enabling the formation of trifluoromethyl compounds from acyl fluorides has been developed. The combination of FLUOLEAD and Olah's reagent in solvent-free conditions at 70 °C initiated the significant deoxyfluorination of the acyl fluorides and resulted in the corresponding trifluoromethyl products with high yields (up to 99%). This strategy showed a great tolerance for various acyl fluorides containing aryloyl, (heteroaryl)oyl, or aliphatic acyl moieties, providing good to excellent yields of the trifluoromethyl products. Synthetic drug-like molecules were also transformed into the corresponding trifluoromethyl compounds under the same reaction conditions. A reaction mechanism is proposed.
- Liang, Yumeng,Taya, Akihito,Zhao, Zhengyu,Saito, Norimichi,Shibata, Norio
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p. 3052 - 3058
(2021/01/15)
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- A methylation platform of unconventional inert aryl electrophiles: Trimethylboroxine as a universal methylating reagent
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Methylation is one of the most fundamental conversions in medicinal and material chemistry. Extension of substrate types from aromatic halides to other unconventional aromatic electrophiles is a highly important yet challenging task in catalytic methylation. Disclosed herein is a series of transition metal-catalyzed methylations of unconventional inert aryl electrophiles using trimethylboroxine (TMB) as the methylating reagent. This transformation features a broad substrate type, including nitroarenes, benzoic amides, benzoic esters, aryl cyanides, phenol ethers, aryl pivalates and aryl fluorides. Another important merit of this work is that these widespread "inert"functionalities are capable of serving as directing or activating groups for selective functionalization of aromatic rings before methylation, which greatly expands the connotation of methylation chemistry.
- Feng, Boya,Yang, Yudong,You, Jingsong
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p. 6031 - 6035
(2020/07/10)
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- Nickel/Photoredox-Catalyzed Methylation of (Hetero)aryl Chlorides Using Trimethyl Orthoformate as a Methyl Radical Source
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Methylation of organohalides represents a valuable transformation, but typically requires harsh reaction conditions or reagents. We report a radical approach for the methylation of (hetero)aryl chlorides using nickel/photoredox catalysis wherein trimethyl orthoformate, a common laboratory solvent, serves as a methyl source. This method permits methylation of (hetero)aryl chlorides and acyl chlorides at an early and late stage with broad functional group compatibility. Mechanistic investigations indicate that trimethyl orthoformate serves as a source of methyl radical via β-scission from a tertiary radical generated upon chlorine-mediated hydrogen atom transfer.
- Kariofillis, Stavros K.,Shields, Benjamin J.,Tekle-Smith, Makeda A.,Zacuto, Michael J.,Doyle, Abigail G.
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supporting information
p. 7683 - 7689
(2020/04/22)
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- METHOD FOR MANUFACTURING DIFLUOROMETHYLENE COMPOUND
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The problem to be solved by the present invention is to provide a novel method for producing a difluoromethylene compound. This problem is solved by a method for producing a difluoromethylene compound containing a —CF2— moiety, the method comprising step A of mixing: a) a carbonyl compound containing a —C(O)— moiety;b) optionally an amine;c) a fluoride represented by the formula: MF, wherein M represents a Group 1 element of the periodic table;d) a halogenated fluorine compound represented by the formula: XFn, wherein X represents chlorine, bromine, or iodine, and n is a natural number of 1 to 5; ande) sulfur chloride.
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Paragraph 0219-0223
(2020/03/28)
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- Mechanism of Photoredox-Initiated C-C and C-N Bond Formation by Arylation of IPrAu(I)-CF3 and IPrAu(I)-Succinimide
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Herein, we report on the photoredox-initiated gold-mediated C(sp2)-CF3 and C(sp2)-N coupling reactions. By adopting gold as a platform for probing metallaphotoredox catalysis, we demonstrate that cationic gold(III) complexes are the key intermediates of the C-C and C-N coupling reactions. The high-valent gold(III) intermediates are accessed by virtue of photoredox catalysis through a radical chain process. In addition, the bond-forming step of the coupling reactions is the reductive elimination from cationic gold(III) intermediates, which is supported by isolation and crystallographic characterization of key Au(III) intermediates.
- Kim, Suhong,Toste, F. Dean
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p. 4308 - 4315
(2019/01/25)
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- Phosphonic acid mediated practical dehalogenation and benzylation with benzyl halides
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For the first time, by using H3PO3/I2 system, various benzyl chlorides, bromides and iodides were dehalogenated successfully. In the presence of H3PO3, benzyl halides underwent electrophilic substitution reactions with electron-rich arenes, leading to a broad range of diarylmethanes in good yields. These transformations feature green, cheap reducing reagents and metal-free conditions. A possible mechanism was proposed.
- Gao, Jing,Han, Li-Biao,Ma, Yonghao,Tang, Zilong,Wu, Xiaofang,Xiao, Jing
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p. 22343 - 22347
(2019/07/31)
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- Hydrodehalogenation of alkyl halides catalyzed by a trichloroniobium complex with a redox active α-diimine ligand
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A high-valent d0 niobium(v) complex, (α-diimine)NbCl3 (1), bearing a dianionic redox-active α-diimine ligand served as a catalyst for a hydrodehalogenation reaction of alkyl halides in the presence of PhSiH3. During the catalytic reaction, the redox-active α-diimine ligand allowed the complex to reversibly release and accept one-electron through switching its coordination mode between a dianionic folded form and a monoanionic planar one.
- Nishiyama, Haruka,Hosoya, Hiromu,Parker, Bernard F.,Arnold, John,Tsurugi, Hayato,Mashima, Kazushi
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p. 7247 - 7250
(2019/07/02)
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- Cathodic C-H Trifluoromethylation of Arenes and Heteroarenes Enabled by an in Situ-Generated Triflyltriethylammonium Complex
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While several trifluoromethylation reactions involving the electrochemical generation of CF3 radicals via anodic oxidation have been reported, the alternative cathodic, reductive radical generation has remained elusive. Herein, the first cathodic trifluoromethylation of arenes and heteroarenes is reported. The method is based on the electrochemical reduction of an unstable triflyltriethylammonium complex generated in situ from inexpensive triflyl chloride and triethylamine, which produces CF3 radicals that are trapped by the arenes on the cathode surface.
- Cantillo, David,Jud, Wolfgang,Kappe, C. Oliver,Maljuric, Snjezana
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supporting information
(2019/10/08)
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- Chemoselective Hydrodeoxygenation of Carboxylic Acids to Hydrocarbons over Nitrogen-Doped Carbon-Alumina Hybrid Supported Iron Catalysts
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The establishment of catalyst systems for the chemoselective hydrodeoxygenation (HDO) of carboxylic acids to hydrocarbons, such as the HDO of long-chain fatty acids to alkanes, is important for biomass to biofuel conversion. As the most abundant and probably the cheapest transition metal on the earth, iron is a promising non-noble-metal alternative to precious metals for large-scale conversion of biomass. However, it usually suffers from unsatisfactory activity. In this work, a nitrogen-doped carbon-alumina hybrid supported iron (Fe-N-C@Al2O3) catalyst is established for chemoselective HDO of carboxylic acids to hydrocarbons. By using stearic acid HDO as the model reaction, n-octadecane and n-heptadecane are produced with yields of 91.9% and 6.0%, respectively. Triglycerides can also be converted into liquid alkanes with a total molar yield of >92%. In addition, the iron catalyst can chemoselectively catalyze the HDO of the carboxylic acid group in the presence of other functional groups such as an aromatic ring. This chemoselectivity has rarely been seen before because the aromatic ring is usually more easily hydrogenated in comparison to HDO of the carboxylic acid group. The characterization results showed that both the formation of a nitrogen-doped carbon-alumina hybrid and the iron loading are important for the Lewis basicity of these catalysts, in order to adsorb the acid substrates. The addition of melamine as the nitrogen precursor during pyrolysis eliminates undesired reactions between the iron precursor and alumina support to form an inactive hercynite phase, leading to the formation of an Fe3C active phase for the hydrogenation of -COOH to -CH2OH and the hybrid of N-C and alumina for the HDO of -CH2OH to -CH3.
- Li, Jiang,Zhang, Junjie,Wang, Shuai,Xu, Guangyue,Wang, Hao,Vlachos, Dionisios G.
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p. 1564 - 1577
(2019/02/03)
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- Ligand-free trifluoromethylation of iodoarenes by use of 2-Aryl-2-trifluoromethylbenzimidazoline as new trifluoromethylating reagent
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N-Methyl 2-aryl-2-trifluoromethylbenzimidazolines were synthesized and utilized in the trifluoromethylation reaction of iodoarenes in the presence of copper(I) salt and base. Iodoarenes bearing electron-donating and electron-withdrawing groups were tolerant to this reaction in the absence of a ligand and gave trifluorotoluene derivatives in good to high yields.
- Miyagawa, Masamichi,Ishikawa, Taisuke,Shinkai, Kota,Akiyama, Takahiko
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supporting information
p. 29 - 31
(2019/01/04)
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- Isolation of OH-bridged Ag(i)/Cu(iii) and ion-pair Cu(i)/Cu(iii) trifluoromethyl complexes with monophosphines
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Cu(iii)-CF3 complexes are important intermediates of both synthetic and mechanistic interest. This study describes the isolation, and spectroscopic and X-ray crystallographic characterization of CuIII-CF3 complexes 2-4 with typical monophosphine ligands PPh3 and Buchwald-type biarylmonophosphines. Distinct from the ion-pair [P2Cu(i)]+[Cu(iii)(CF3)4]? structures of 2 and 4 (P: PPh3 or SPhos), complex 3 exhibits a novel OH-bridged Ag(i)-Cu(iii) dinuclear structure with XPhos-coordinated linear Ag(i) and square planar Cu(iii) components. This is the first heterobimetallic Cu(iii)-CF3 complex confirmed by both solution-phase NMR spectroscopy and solid state X-ray crystal structure analysis. Complex 3 is found to have the LUMO orbital of major σ*(Cu-CF3) nature and electrophilic CF3 ligands. Accordingly, complex 3 is able to trifluoromethylate 2 equivalents of aryl boronic acids in up to quantitative yields, regardless of the inert or oxidative conditions. In contrast, the ion-pair complexes 2 and 4 show low reactivity. This study enriches the coordination and reactivity chemistry of Cu(iii)-CF3 compounds and shows the feasibility of modulation of structures and reactivity by ligand design, which may inspire future efforts on Cu(iii)-CF3 chemistry.
- Xiao, Chang,Zhang, Song-Lin
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supporting information
p. 848 - 853
(2019/01/21)
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- Iron-catalyzed cross coupling of aryl chlorides with alkyl Grignard reagents: Synthetic scope and FeII/FeIV mechanism supported by x-ray absorption spectroscopy and density functional theory calculations
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A combination of iron(III) fluoride and 1,3-bis(2,6-diiso-propylphenyl)imidazolin-2-ylidene (SIPr) catalyzes the high-yielding cross coupling of an electron-rich aryl chloride with an alkyl Grignard reagent, which cannot be attained using other iron catalysts. A variety of alkoxy-or amino-substituted aryl chlorides can be cross-coupled with various alkyl Grignard reagents regardless of the presence or absence of β-hydrogens in the alkyl group. A radical probe experiment using 1-(but-3-enyl)-2-chlorobenzene does not afford the corresponding cyclization product, therefore excluding the intermediacy of radical species. Solution-phase X-ray absorption spectroscopy (XAS) analysis, with the help of density functional theory (DFT) calculations, indicates the formation of a high-spin (S = 2) heteroleptic difluorido organoferrate(II), [MgX][FeIIF2(SIPr)-(Me/alkyl)], in the reaction mixture. DFT calculations also support a feasible reaction pathway, including the formation of a difluorido organoferrate(II) intermediate which undergoes a novel Lewis acid-assisted oxidative addition to form a neutral organoiron(IV) intermediate, which leads to an FeII/FeIV cata-lytic cycle, where the fluorido ligand and the magnesium ion play key roles.
- Agata, Ryosuke,Takaya, Hikaru,Matsuda, Hiroshi,Nakatani, Naoki,Takeuchi, Katsuhiko,Iwamoto, Takahiro,Hatakeyama, Takuji,Nakamura, Masaharu
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supporting information
p. 381 - 390
(2019/02/25)
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- Generation of Phosphoranyl Radicals via Photoredox Catalysis Enables Voltage-Independent Activation of Strong C-O Bonds
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Despite the prevalence of alcohols and carboxylic acids as functional groups in organic molecules and the potential to serve as radical precursors, C-O bonds remain difficult to activate. We report a synthetic strategy for direct access to both alkyl and acyl radicals from these ubiquitous functional groups via photoredox catalysis. This method exploits the unique reactivity of phosphoranyl radicals, generated from a polar/SET crossover between a phosphine radical cation and an oxygen-centered nucleophile. We show the desired reactivity in the reduction of benzylic alcohols to the corresponding benzyl radicals with terminal H atom trapping to afford the deoxygenated products. Using the same method, we demonstrate access to synthetically versatile acyl radicals, which enables the reduction of aromatic and aliphatic carboxylic acids to the corresponding aldehydes with exceptional chemoselectivity. This protocol also transforms carboxylic acids to heterocycles and cyclic ketones via intramolecular acyl radical cyclizations to forge C-O, C-N, and C-C bonds in a single step.
- Stache, Erin E.,Ertel, Alyssa B.,Rovis, Tomislav,Doyle, Abigail G.
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p. 11134 - 11139
(2018/11/21)
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- Diverse copper(iii) trifluoromethyl complexes with mono-, bi- and tridentate ligands and their versatile reactivity
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Cu(iii) trifluoromethyl complexes are proposed as essential intermediates for many copper-promoted trifluoromethylation reactions, but remain elusive and scarcely explored. We report herein the isolation and spectroscopic and X-ray crystallographic charac
- Zhang, Song-Lin,Xiao, Chang,Wan, Hai-Xing
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supporting information
p. 4779 - 4784
(2018/04/11)
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- An Additive-Free, Base-Catalyzed Protodesilylation of Organosilanes
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We report an additive-free, base-catalyzed C-, N-, O-, and S-Si bond cleavage of various organosilanes in mild conditions. The novel catalyst system exhibits high efficiency and good functional group compatibility, providing the corresponding products in good to excellent yields with low catalyst loadings. Overall, this transition-metal-free process may offer a convenient and general alternative to current employing excess bases, strong acids, or metal-catalyzed systems for the protodesilylation of organosilanes.
- Yao, Wubing,Li, Rongrong,Jiang, Huajiang,Han, Deman
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p. 2250 - 2255
(2018/02/23)
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- Comparative profiling of well-defined copper reagents and precursors for the trifluoromethylation of aryl iodides
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A number of copper reagents were compared for their effectiveness in trifluoromethylating 4-iodobiphenyl, 4-iodotoluene, and 2-iodotoluene. Yields over time were plotted in order to refine our understanding of each reagent performance, identify any bottlenecks, and provide more insight into the rates of the reactions. Interestingly, differences in reactivity were observed when a welldefined [LCuCF3] complex was employed directly or generated in situ from precursors by published reports. Relative reactivities were also found to highly dependent on the nature of the iodoarenes.
- Kaplan, Peter T.,Lloyd, Jessica A.,Chin, Mason T.,Vicic, David A.
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p. 2297 - 2303
(2017/11/16)
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- Manganese-Catalyzed Direct Deoxygenation of Primary Alcohols
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Deoxygenation of alcohols is an important tool in the repertoire of defunctionalization methods in modern synthetic chemistry. We report the base-metal-catalyzed direct deoxygenation of benzylic and aliphatic primary alcohols via oxidative dehydrogenation/Wolff-Kishner reduction. The reaction is catalyzed by a well-defined PNP pincer complex of Earth-abundant manganese, evolving H2, N2, and water as the only byproducts.
- Bauer, Jonathan O.,Chakraborty, Subrata,Milstein, David
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p. 4462 - 4466
(2017/07/24)
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- Copper-Promoted Conversion of Aromatic Amines into Trifluoromethylated Arenes: One-Pot Sandmeyer Trifluoromethylation
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A simple copper-promoted one-pot Sandmeyer trifluoromethylation of aromatic amines with Langlois’ reagent has been demonstrated. The reaction is performed in mild reaction conditions under an air atmosphere with good substrate scope and functional group compatibility. It provides an alternative and straightforward synthetic approach to access a variety of trifluoromethylated arenes.
- Hong, Jianquan,Wang, Guifu,Huo, Lianguang,Zheng, Changge
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supporting information
p. 1761 - 1767
(2017/09/06)
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- A method for synthesis of methyl benzotrifluoride
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A synthesis method of methyl benzotrifluoride belongs to the field of chemical synthesis. The method uses 2,5-dichlorotoluene as a starting material, and includes the steps of: (1) a Friedel-Crafts reaction; (2) a fluorination reaction; (3) a hydrodechlorination reaction, and final synthesis of the target products methyl benzotrifluoride. The synthesis method of methyl benzotrifluoride uses extensive sources of raw materials at low price; the reactions involved are mature reactions in the industry; the prepared final product has the content of the methyl benzotrifluoride higher than 99 % and contains less impurities; and the product has stable quality and performance. The total yield of methyl benzotrifluoride in the process is 60% or more. The invention has the advantages of simple reaction conditions, high yield and high product purity, and is applicable to industrial production.
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Paragraph 0028; 0035; 0036
(2017/10/25)
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- Phosphovanadomolybdic acid catalyzed direct C-H trifluoromethylation of (hetero)arenes using NaSO2CF3 as the CF3 source and O2 as the terminal oxidant
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A direct C-H trifluoromethylation of (hetero)arenes using NaSO2CF3 (Langlois' reagent) as the CF3 source and O2 as the terminal oxidant has been developed. In the presence of catalytic amounts of phosphovanadomolybdic acids, such as H6PV3Mo9O40, various kinds of substituted benzenes and heteroaromatic compounds could be converted into the corresponding trifluoromethylated products.
- Li, Chifeng,Suzuki, Kosuke,Yamaguchi, Kazuya,Mizuno, Noritaka
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supporting information
p. 1417 - 1420
(2017/02/23)
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- Trifluoroacetic acid copper (I) reagent and its application in the trifluoromethylation reaction
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The invention discloses a copper trifluoroacetate (I) reagent and application thereof in trifluoromethylate reaction. The structural formula is disclosed in the specification. The copper trifluoroacetate (I) reagent is prepared by the following steps: reacting cuprous chloride, sodium tert-butyl alcoholate and bidentate nitrogen ligand in a tetrahydrofuran solvent, adding trifluoroacetic acid to react, and finally, carrying out separation purification to obtain the copper trifluoroacetate (I) reagent. The reagent can perform trifluoromethylation reaction with halogenated aromatic hydrocarbons or halogenated heterocyclic compounds in a decarboxylation mode to form the corresponding trifluoromethylation derivates. The method has the advantages of simple preparation technique and cheap and accessible raw materials; and the obtained copper trifluoroacetate (I) reagent has favorable selectivity, can promote the trifluoromethylation reaction to proceed quickly and efficiently, and has favorable industrial application prospects.
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Paragraph 0029; 0030
(2017/03/25)
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- Nickel-catalyzed C-N bond reduction of aromatic and benzylic quaternary ammonium triflates
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A nickel-catalyzed, efficient C-N bond reduction of aromatic and benzylic ammonium triflates has been developed using sodium isopropoxide as a reducing agent. The high efficiency, mild conditions, and good compatibility with various substituents made this method an effective supplement to the current catalytic hydrogenation reactions. Combining this reductive deamination reaction with directed aromatic functionalization reactions, a powerful strategy for regioselective functionalization of arenes was demonstrated using dialkylamine groups as traceless directing groups.
- Yi, Yuan-Qiu-Qiang,Yang, Wen-Cheng,Zhai, Dan-Dan,Zhang, Xiang-Yu,Li, Shuai-Qi,Guan, Bing-Tao
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p. 10894 - 10897
(2016/09/09)
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- DBU-Promoted Trifluoromethylation of Aryl Iodides with Difluoromethyltriphenylphosphonium Bromide
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DBU-promoted trifluoromethylation of aryl iodides with difluoromethyltriphenylphosphonium bromide (DFPB) in the presence of copper source is described. In this transformation, DBU not only acts as base to deprotonate the difluoromethyl group in DFPB to generate difluoromethylene phosphonium ylide Ph3P+CF2-, but also converts the difluorocarbene generated from ylide Ph3P+CF2- into trifluoromethyl anion, finally resulting in the trifluoromethylation of aryl iodides. The reactions proceeded smoothly to afford expected products in moderate to good yields.
- Wei, Yun,Yu, Liuying,Lin, Jinhong,Zheng, Xing,Xiao, Jichang
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p. 481 - 484
(2016/06/01)
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- Trifluoromethylation of haloarenes with a new trifluoro-methylating reagent Cu(O2CCF2SO2F)2
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A new trifluoromethylating reagent Cu(O2CCF2SO2F)2, which easily decomposes to generate active CuCF3 species in DMF at room temperature, has been conveniently prepared from inexpensive starting materials on a large scale. This new reagent can be applied to efficiently trifluoromethylate a variety of haloarenes under mild conditions, providing good-to-excellent yields of the desired products.
- Zhao, Gang,Wu, Hao,Xiao, Zhiwei,Chen, Qing-Yun,Liu, Chao
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p. 50250 - 50254
(2016/06/15)
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- Copper-catalysed synthesis of trifluoromethyl(hetero)arenes from di(hetero)aryl-λ3-iodanes
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An efficient synthesis of trifluoromethylated (hetero)arenes has been achieved through the regioselective copper-catalyzed trifluoromethylation of di(hetero)aryl-λ3-iodanes, employing readily available trifluoromethyltrimethylsilane. The reaction works well for both symmetrical and unsymmetrical di(hetero)aryl-λ3-iodanes with good regioselectivity and also tolerates diverse functional groups such as bromo, iodo, cyano, nitro, ester, ketone and enolizable ketone.
- Pandey, Vinay Kumar,Anbarasan, Pazhamalai
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p. 18525 - 18529
(2016/02/27)
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- Decarboxylative Trifluoromethylating Reagent [Cu(O2CCF3)(phen)] and Difluorocarbene Precursor [Cu(phen)2][O2CCF2Cl]
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This article describes the new economic decarboxylative trifluoromethylating reagent [Cu(phen)(O2CCF3)] (1; phen=1,10-phenanthroline) and the efficient difluorocarbene precursor [Cu(phen)2][O2CCF2Cl] (2). Treatment of copper tert-butoxide with phen and subsequent addition of trifluoroacetic acid or chlorodifluoroacetic acid afforded air-stable complexes 1 and 2, respectively, which were characterized by X-ray crystallography. The copper(I) ion in 1 is coordinated by a bidentate phen ligand, a monodentate trifluoroacetate group, and a molecule of CH3CN in a distorted tetrahedral coordination geometry. The molecular structure of 2 adopts an ionic form that consists of a [Cu(phen)2]+ cation and a chlorodifluoroacetate anion. Complex 1 reacted with a variety of aryl and heteroaryl halides to form trifluoromethyl (hetero)arenes in good yields. The corresponding Hammett plot exhibited a linear relationship and a reaction parameter (ρ)=+0.56±0.02, which indicated that the trifluoromethylation reaction proceeded via a nucleophilic reactive species. Complex 2 reacts with phenols to produce aryl difluoromethyl ethers in modest-to-excellent yields. Mechanistic investigations revealed that the difluoromethylation reaction proceeds by initial copper-mediated formation of difluorocarbene and subsequent concerted addition of difluorocarbene to the phenol to form a three-center transition state.
- Lin, Xiaoxi,Hou, Chuanqi,Li, Haohong,Weng, Zhiqiang
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supporting information
p. 2075 - 2084
(2016/02/12)
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- TCDA: Practical Synthesis and Application in the Trifluoromethylation of Arenes and Heteroarenes
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A practical synthesis of the reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported on 50 g scale. The trifluoromethylation with TCDA was optimized, and the reaction shows very broad scope with respect to electron-deficient, -neutral, -rich aryl/heteroaryl iodides, as well as excellent functional group tolerability, such as ester, amide, aldehyde, hydroxyl, and carboxylic acid. The reagent was also applied to the late-stage trifluoromethylation of three medicinally relevant compounds. Additionally, the building block trifluoromethylpyridine and one drug related molecule Boc-Fluoxetin were synthesized in 10 g scale by this method, demonstrating its practical applications in process chemistry.
- Wang, Jian,Zhang, Xiaomin,Wan, Zehong,Ren, Feng
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p. 836 - 839
(2016/05/19)
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- Mild Deoxygenation of Aromatic Ketones and Aldehydes over Pd/C Using Polymethylhydrosiloxane as the Reducing Agent
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Herein, a practical and mild method for the deoxygenation of a wide range of benzylic aldehydes and ketones is described, which utilizes heterogeneous Pd/C as the catalyst together with the green hydride source, polymethylhydrosiloxane. The developed catalytic protocol is scalable and robust, as exemplified by the deoxygenation of ethyl vanillin, which was performed on a 30 mmol scale in an open-to-air setup using only 0.085 mol% Pd/C catalyst to furnish the corresponding deoxygenated product in 93% yield within 3 hours at room temperature. Furthermore, the Pd/C catalyst was shown to be recyclable up to 6 times without any observable decrease in efficiency and it exhibited low metal leaching under the reaction conditions.
- Volkov, Alexey,Gustafson, Karl P. J.,Tai, Cheuk-Wai,Verho, Oscar,B?ckvall, Jan-E.,Adolfsson, Hans
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supporting information
p. 5122 - 5126
(2015/04/27)
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- Halide-Dependent Mechanisms of Reductive Elimination from Gold(III)
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Two unique organometallic halide series (Ph3P)Au(4-Me-C6H4)(CF3)(X) and (Cy3P)Au(4-F-C6H4)(CF3)(X) (X = I, Br, Cl, F) have been synthesized. The PPh3-supported complexes can undergo both Caryl-X and Caryl-CF3 reductive elimination. Mechanistic studies of thermolysis at 122 °C reveal a dramatic reactivity and kinetic selectivity dependence on halide ligand. For X = I or F, zero-order kinetic behavior is observed, while for X = Cl or Br, kinetic studies implicate product catalysis. The selectivity for Caryl-CF3 bond formation increases in the order X = I aryl-I bond formation when X = I, and exclusively Caryl-CF3 bond formation when X = F. Thermodynamic measurements show that Au(III)-X bond dissociation energies increase in the order X = I aryl-X and Caryl-CF3 reductive elimination. (Graph Presented).
- Winston, Matthew S.,Wolf, William J.,Toste, F. Dean
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supporting information
p. 7921 - 7928
(2015/07/02)
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- Mixed-ligand complexes of paddlewheel dinuclear molybdenum as hydrodehalogenation catalysts for polyhaloalkanes
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We developed a hydrodehalogenation reaction of polyhaloalkanes catalyzed by paddlewheel dimolybdenum complexes in combination with 1-methyl-3,6-bis(trimethylsilyl)-1,4-cyclohexadiene (MBTCD) as a non-toxic H-atom source as well as a salt-free reductant. A mixed-ligated dimolybdenum complex Mo2(OAc)2[CH(NAr)2]2 (3a, Ar = 4-MeOC6H4) having two acetates and two amidinates exhibited high catalytic activity in the presence of nBu4NCl, in which [nBu4N]2[Mo2{CH(NAr)2}2Cl4] (9a), derived by treating 3a with ClSiMe3 and nBu4NCl, was generated as a catalytically-active species in the hydrodehalogenation. All reaction processes, oxidation and reduction of the dimolybdenum complex, were clarified by control experiments, and the oxidized product, [nBu4N][Mo2{CH(NAr)2}2Cl4] (10a), was characterized by EPR and X-ray diffraction studies. Kinetic analysis of the hydrodehalogenation reaction as well as a deuterium-labelling experiment using MBTCD-d8 suggested that the H-abstraction was the rate-determining step for the catalytic reaction. This journal is
- Tsurugi, Hayato,Hayakawa, Akio,Kando, Shun,Sugino, Yoshitaka,Mashima, Kazushi
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p. 3434 - 3439
(2015/05/27)
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- Introducing a new radical trifluoromethylation reagent
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Perfluoro-3-ethyl-2,4-dimethyl-3-pentyl radical (PPFR) is a persistent radical stable at room temperature, but easily decomposes at 90 °C to produce a CF3 radical which is able to react with a variety of aromatic compounds to afford the corresponding trifluoromethyl derivatives, usually as mixtures of regioisomers in good to excellent overall yields.
- Sato, Azusa,Han, Jianlin,Ono, Taizo,Wzorek, Alicja,Ace?a, José Luis,Soloshonok, Vadim A.
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supporting information
p. 5967 - 5970
(2015/03/30)
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- METHOD FOR PRODUCING ORGANIC COMPOUND
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PROBLEM TO BE SOLVED: To provide a method of subjecting a compound having on one carbon atom a carbon atom constituting a carbon-carbon double bond and a functional group such as a hydroxyl group to a reductive reaction condition and producing an organic compound having the functional group substituted with a hydrogen atom. SOLUTION: There is provided a method for producing a compound represented by a formula (50) from a raw material compound represented by a formula (10). The method includes a step of irradiating a reaction system with light, the reaction system comprising the raw material compound, a hydrogen source compound, and a catalyst having a palladium component supported by a carrier containing titanium oxide. (R11 to R15 are a hydrogen atom, a hydrocarbon group having 1 to 40 carbon atoms which may have a cyclic structure or a derivative group thereof, or a heteroatom-containing group having 1 to 20 carbon atoms which may have a cyclic structure or a derivative group thereof; and R16 is a hydrogen atom, a hydrocarbon group having 1 to 40 carbon atoms or an acyl group having 1 to 20 carbon atoms which may have a cyclic structure, or -CH(CH2OH)2).) COPYRIGHT: (C)2015,JPO&INPIT
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Paragraph 0095; 0097-0101
(2018/10/16)
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- Preparation of an Arenylmethylzinc Reagent with Functional Groups by Chemoselective Cross-Coupling Reaction of Bis(iodoazincio)methane with Iodoarenes
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Palladium-catalyzed cross-coupling reaction of bis(iodozincio)methane with iodoarenes carrying various functionalities such as ester, boryl, cyano, and halo groups proceeded chemoselectively to give the corresponding arenylmethylzinc species efficiently. The moderate reactivity of the gem-dizinc reagent imparted functional group tolerance to the process. The transformations from iodoheteroarenes were also performed; in the case of iodopyridine derivatives, the nickel-catalyzed reaction gave the corresponding organozinc species efficiently. The obtained arenylmethylzinc species underwent the copper-mediated coupling reaction with a range of organic halides.
- Shimada, Yukako,Haraguchi, Ryosuke,Matsubara, Seijiro
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p. 2395 - 2398
(2015/10/19)
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- Oxidation of Ni(II) to Ni(IV) with Aryl Electrophiles Enables Ni-Mediated Aryl-CF3 Coupling
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This communication describes the synthesis and reactivity of NiIV(aryl)(CF3)2 complexes supported by trispyrazolylborate and 4,4′-di-tert-butylbipyridine ligands. We demonstrate that isolable NiIV complexes can be accessed under mild conditions via the oxidation of NiII precursors with S-(trifluoromethyl)dibenzothiophenium triflate as well as with diaryliodonium and aryl diazonium reagents. The NiIV intermediates undergo high yielding aryl-CF3 bond-forming reductive elimination. These studies support the potential viability of NiIV intermediates in nickel-catalyzed coupling reactions involving diaryliodonium and aryldiazonium electrophiles.
- Bour, James R.,Camasso, Nicole M.,Sanford, Melanie S.
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supporting information
p. 8034 - 8037
(2015/07/08)
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- Iron fluoride/N-heterocyclic carbene catalyzed cross coupling between deactivated aryl chlorides and alkyl grignard reagents with or without β-hydrogens
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High-yielding cross-coupling reactions of various combinations of aryl chlorides and alkyl Grignard reagents have been developed by using an iron(III) fluoride/1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene (SIPr) catalyst composite. The iron(III) fluoride/SIPr-catalyzed aryl-alkyl coupling demonstrates unprecedented scope for both aryl chlorides and alkyl Grignard reagents, thus enabling the first efficient coupling of electron-rich (deactivated) aryl chlorides with alkyl Grignard reagents without β-hydrogens. The present reaction is also effective for diverse alkyl Grignard reagents such as (trimethylsilyl)methyl, primary, and secondary alkyl Grignard reagents.
- Agata, Ryosuke,Iwamoto, Takahiro,Nakagawa, Naohisa,Isozaki, Katsuhiro,Hatakeyama, Takuji,Takaya, Hikaru,Nakamura, Masaharu
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p. 1733 - 1740
(2015/06/16)
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- New Reagent for Highly Efficient Synthesis of Trifluoromethyl-Substituted Arenes and Heteroarenes
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A new reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported for the introduction of a -CF3 group to arenes and heteroarenes. Compared with current known reagents, TCDA shows very broad scope with respect to electron-deficient, -neutral, and -rich aryl/heteroaryl iodides as well as excellent functional group tolerance, including ester, amide, aldehyde, hydroxyl, and carboxylic acid. (Chemical Equation Presented).
- Zhang, Xiaomin,Wang, Jian,Wan, Zehong
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supporting information
p. 2086 - 2089
(2015/05/13)
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- Copper-mediated trifluoromethylation using phenyl trifluoromethyl sulfoxide
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A new method for the generation of trifluoromethylcopper ( CuCF3 ) species from readily available phenyl trifluoromethyl sulfoxide has been developed. The CuCF3 reagent can be applied in efficient trifluoromethylations of aryl iodides and activated aryl bromides in the absence of additional ligands. Furthermore, the CuCF3 species can also undergo oxidative cross-coupling with terminal alkynes and arylboronic acids.
- Li, Xinjin,Zhao, Jingwei,Zhang, Liang,Hu, Mingyou,Wang, Limin,Hu, Jinbo
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supporting information
p. 298 - 301
(2015/03/04)
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- One-pot sandmeyer trifluoromethylation and trifluoromethylthiolation
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Practical one-pot procedures were developed for both Sandmeyer-type trifluoromethylations and trifluoromethylthiolations. Starting from broadly available (hetero)aromatic amines, various benzotrifluorides were synthesized in high yields via in situ diazotization and copper-mediated trifluoromethylation using the inexpensive Ruppert-Prakash trifluoromethylating reagent. In the presence of sodium thiocyanate as a sulfur source, aryl trifluoromethyl thioethers are exclusively formed.
- Bayarmagnai, Bilguun,Matheis, Christian,Risto, Eugen,Goossen, Lukas J.
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supporting information
p. 2343 - 2348
(2014/07/21)
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- Copper-mediated trifluoromethylation of aryl-, heteroaryl-, and vinyltrifluoroborates with Langlois' reagent
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An effortless and realistic procedure for the copper-mediated trifluoromethylation of aryl-, heteroaryl- and vinyltrifluoroborates with CF3 radicals generated from NaSO2CF3 and tert-butyl hydroperoxide (TBHP) is presented. The developed method produces trifluoromethyl arenes and -alkenes in good to excellent yields and a wide range of electronically and structurally diverse substrates are tolerated.
- Dubbaka, Srinivas Reddy,Salla, Manohar,Bolisetti, Raghu,Nizalapur, Shashidhar
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p. 6496 - 6499
(2014/02/14)
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- Trifluoromethylation of arenediazonium salts with fluoroform-derived CuCF3 in aqueous media
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A new protocol has been developed for trifluoromethylation of arenediazonium salts with moisture-sensitive CuCF3 (from fluoroform) in aqueous media. The reaction is governed by a radical mechanism, tolerates a broad variety of functional groups, and is applicable to the synthesis of complex, polyfunctionalized molecules. This journal is the Partner Organisations 2014.
- Lishchynskyi, Anton,Berthon, Guillaume,Grushin, Vladimir V.
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supporting information
p. 10237 - 10240
(2014/08/18)
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- Cross alkyl-aryl versus homo aryl-aryl coupling in palladium-catalyzed coupling of alkyl-gold(I) and aryl-halide
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Experiments on palladium-catalyzed cross-coupling of [AuMe(PPh 3)] with aryl iodides show that Ar-Ar homocoupling products are the main product or an abundant byproduct of the reaction. The percentage of cross-coupling product is higher for aryls with a larger σp Hammet parameter. The scrambling of organic groups via bimetallic intermediates explains the formation of these products. This scrambling can be observed and the activation energies partially quantified in some cases using as aryl C 6Cl2F3, which is relatively reluctant to coupling.
- Carrasco, Desiree,Perez-Temprano, Monica H.,Casares, Juan A.,Espinet, Pablo
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p. 3540 - 3545
(2014/08/05)
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- Mechanism of trifluoromethylation of aryl halides with CuCF3and the ortho effect
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A combined experimental (radical clock, kinetic, Hammett) and computational (DFT, MM) study of the trifluoromethylation reaction of aryl halides with CuCF3 reveals a nonradical mechanism involving Ar-X oxidative addition to the Cu(I) center as the rate determining step. The reaction is second order, first order in each reactant with ΔG? ≈ 24 kcal/mol for PhI (computed ΔG? = 21.9 kcal/ mol). An abrupt change in the gradient on the Hammett plot of log(kR/ kH) versus σp for 11 p-RC6H4I substrates produces two correlations (ρ = +0.69 and +1.83), which is temptingly suggestive of two different reaction pathways. Only one mechanism is operational, however, as advocated by a single linear correlation with σp- (ρ = +0.91), analysis of the experimental ρ values, close similarity of the transition states varying in R and displaying clear signs of -M interactions, and excellent reproduction of the plot by DFT. The long-known yet previously uncomprehended ortho effect has been quantified, for the first time, using the reaction of CuCF3 with a series of o-RC6H4Br: R(kR/kH) = H (1) 2Me (850) 2 (4300) 2H (150 000). With minor contributions from electronic factors, the ortho effect is largely determined by (i) the stabilizing coordination of the o-substituent to Cu in the transition state with the Cu?O distance varying directly with the barrier and (ii) the steric bulk of the o-substituent that raises the ground state free energy of the haloarene (Go ortho - Go H or Go ortho - Go para) by inflicting molecular strain and consequently weakening the Ar-X bond.
- Konovalov, Andrey I.,Lishchynskyi, Anton,Grushin, Vladimir V.
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supporting information
p. 13410 - 13425
(2015/03/30)
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- Trifluoromethylation of aryl and heteroaryl halides with fluoroform-derived CuCF3: Scope, limitations, and mechanistic features
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Fluoroform-derived CuCF3 recently discovered in our group exhibits remarkably high reactivity toward aryl and heteroaryl halides, performing best in the absence of extra ligands. A broad variety of iodoarenes undergo smooth trifluoromethylation with the ligandless CuCF3 at 23-50 C to give the corresponding benzotrifluorides in nearly quantitative yield. A number of much less reactive aromatic bromides also have been trifluoromethylated, including pyridine, pyrimidine, pyrazine, and thiazole derivatives as well as aryl bromides bearing electron-withdrawing groups and/or ortho substituents. Only the most electrophilic chloroarenes can be trifluoromethylated, e.g., 2-chloronicotinic acid. Exceptionally high chemoselectivity of the reactions (no side-formation of arenes, biaryls, and C2F5 derivatives) has allowed for the isolation of a large number of trifluoromethylated products in high yield on a gram scale (up to 20 mmol). The CuCF3 reagent is destabilized by CuX coproduced in the reaction, the magnitude of the effect paralleling the Lewis acidity of CuX: CuCl > CuBr > CuI. While SNAr and SRN1 mechanisms are not operational, there is a well-pronounced ortho effect, i.e., the enhanced reactivity of ortho-substituted aryl halides 2-RC6H4X toward CuCF3. Intriguingly, this ortho-effect is observed for R = NO2, COOH, CHO, COOEt, COCH3, OCH3, and even CH3, but not for R = CN. The fluoroform-derived CuCF3 reagent and its reactions with haloarenes provide an unmatched combination of reactivity, selectivity, and low cost.
- Lishchynskyi, Anton,Novikov, Maxim A.,Martin, Eddy,Escudero-Adan, Eduardo C.,Novak, Petr,Grushin, Vladimir V.
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p. 11126 - 11146
(2013/12/04)
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- Copper-catalyzed trifluoromethylation of aryl- and vinylboronic acids with generation of CF3-radicals
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The selective trifluoromethylation of aryl- and vinylboronic acids proceeds smoothly with CF3SO2Na (Langlois reagent) in the presence of copper catalysts and t-BuOOH. Therefore, the method relies both on transition metal catalysis an
- Li, Yang,Wu, Lipeng,Neumann, Helfried,Beller, Matthias
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supporting information
p. 2628 - 2630
(2013/04/23)
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- CuI-mediated trifluoromethylations with stannanes. preliminary communication
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(Trifluoromethyl)stannane reagents such as Bu3SnCF3 are effective in CuI-mediated trifluoromethylation reactions of aryl iodides. The reactions proceed via the intermediacy of [CuCF3] species.
- Sanhueza, Italo A.,Nielsen, Mads C.,Ottiger, Marcel,Schoenebeck, Franziska
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p. 2231 - 2236
(2013/02/22)
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- Intermolecular photodecarboxylation of electron-deficient substrates by phthalimides in water: Efficiency, selectivity and online monitoring
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The intermolecular photodecarboxylation of arylacetic acids 3-5 in water by use of stoichiometric amounts of N-alkylated phthalimides 1a,b was investigated by NMR and online pH- and CO2-release sensing. Decreasing the electron donor capability of the arylacetic acids by 4-fluoro and trifluoromethyl substitution alters the efficiency of the photodecarboxylation and selectivity of the secondary reaction. A remarkable switch in reaction channel (A to B) was observed for perfluoropropionic acid.
- Griesbeck, Axel G.,Nazarov, Nestor,Neudoerfl, Joerg M.,Heffen, Maria
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p. 3004 - 3006
(2013/01/15)
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- Practical method for the Cu-mediated trifluoromethylation of arylboronic acids with CF3 radicals derived from NaSO2CF3 and tert-butyl hydroperoxide (TBHP)
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A mild and practical protocol for the copper-mediated trifluoromethylation of aryl and heteroaryl boronic acids using NaSO2CF3 (Langlois' reagent) and TBHP is described. The reaction proceeds at room temperature under ambient conditions, and the products can be readily purified by extraction or column chromatography.
- Ye, Yingda,Kuenzi, Stefan A.,Sanford, Melanie S.
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supporting information
p. 4979 - 4981,3
(2012/12/12)
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